Effect of RMGI Roughness and Dentin Bonding Primer on Shear Bond Strength of Sandwich-type Restorations.

BACKGROUND: The open sandwich technique is a reliable alternative to amalgam placement in deep proximal box preparations, where proper isolation and enamel bonding may not be possible. It is often difficult to prepare the box for composite placement without affecting the resin-modified glass ionomer (RMGI) that has been placed in the gingival portion. We hypothesized that RMGI surfaces that are roughened or those that use all steps in the manufacturing bonding protocol, including the priming solution, applied before placing a bonded composite increment, would have greater composite/RMGI shear bond strength. DESIGN AND METHODS: Shear bond strengths (SBS) of RMGI tested in the presence and absence of SiC roughening and primer-coating were tested using a fourth-generation dentin bonding agent to composite after thermocycling. Twenty specimens for four test conditions were fabricated and investigated. Data were subjected to a two-way ANOVA and the Holm-Sidak post-hoc test. RESULTS: Placing dentin primer on unabraded RMGI provided a statistically significant improvement in SBS, but only modestly. Furthermore, because bond failure consistently occurred within the RMGI itself, none of the surface modifications have a clinically relevant impact on SBS at the RMGI to the composite interface. CONCLUSIONS: Clinicians should be aware that they need not avoid RMGI abrasion and do not need to incorporate all components of a fourth-generation bonding system when covering an RMGI sandwich layer with composite.

Neurological symptoms associated with SARS-CoV-2 infection in a tertiary hospital in Bogota, Colombia.

Introduction: SARS-CoV-2 infection is an emerging disease that represents a threat to life globally, with more than 179 million confirmed cases and 3 million deaths. In Colombia, where almost 5 million infections and approximately 127 thousand deaths have been reported, it presents a wide variety of neurological manifestations that range from mild to severe symptoms. Objective: This study describes the characteristics of neurological manifestations in patients with COVID-19 in the period March-September 2020 at a tertiary hospital in Bogota. Methods: We performed a cross-sectional descriptive study. We selected patients by non-probability sampling, including all patients attended by the neurology service at our hospital. We included all patients with infection confirmed by RT-PCR test and neurological disease confirmed by tomography, study of cerebrospinal fluid, and clinical manifestations reported in the medical history. We excluded epileptic patients who presented seizures as the only clinical manifestation. Results: In a total of 58 patients, the mean age was 58 years, with 60.3% of patients being men; 65.5% were alert at admission. The main neurological symptom was brain ischaemia, in 36.2%, followed by seizures, in 25.9%. Arterial hypertension was observed in 58.6%. We observed no alterations in the cerebrospinal fluid; the mean hospital stay was 35 days, and 41.4% of patients died. Conclusions: SARS-CoV-2 infection not only affects the respiratory system, but can also cause a range of neurological manifestations ranging from mild symptoms such as headache, dysgeusia, and anosmia to severe complications such as seizures, brain ischaemia/haemorrhage, encephalopathy, or death.

Introducción: La infección por SARS-CoV2 es una enfermedad emergente que representa un peligro para la vida a nivel mundial, con más de 179 millones de casos confirmados y 3 millones de muertes. En Colombia, se han reportado casi 5 millones de personas contagiadas y alrededor de 127 mil fallecidos, presenta una amplia variedad de manifestaciones neurológicas que van desde leves a severas. Objetivo: Describir las características de las manifestaciones neurológicas en pacientes con infección por coronavirus SARS-CoV2 (Covid19) en el periodo marzo ­ septiembre de 2020 en un Hospital de 3er nivel en Bogotá. Metodología: Se trata de un estudio descriptivo tipo corte transversal. Se realizó un muestreo no probabilístico en el que se incluyeron todos los casos atendidos por el servicio de neurología de la institución seleccionada, se incluyeron todos los pacientes con infección confirmada por prueba de RT-PCR y aquellos con enfermedad neurológica documentada por tomografía, estudio de líquido cefalorraquídeo o manifestaciones clínicas registradas en la historia clínica. Fueron excluidos los pacientes epilépticos quienes presenten convulsiones como única manifestación clínica. Resultados: En un total de 58 pacientes, se encontró media de edad de 58 años, con un 60,3% correspondiente al sexo masculino, 65,5% estuvieron alerta, la principal manifestación neurológica fue la isquemia cerebral en un 36,2%, seguida de convulsiones con un 25,9%. La hipertensión arterial estuvo en el 58,6%. No hubo alteraciones en el LCR, el promedio de estancia hospitalaria fue de 35 días y el 41,4% fallecieron. Conclusiones: La infección por SARS-CoV2 condiciona no solo una afección al sistema respiratorio, sino que presenta un amplio espectro de manifestaciones neurológicas que van desde las más leves como cefalea, disgeusia y anosmia, hasta las más graves como convulsiones, isquemia/sangrado cerebral, encefalopatía o muerte.

Occupational asthma and rhinitis due to yellow and red henna in a hairdresser

No disponible

Amino Acid-Functionalized Polyelectrolyte Films as Bioactive Surfaces for Cell Adhesion.

Surfaces were prepared with polyelectrolyte derivatives of poly(styrene- alt-maleic anhydride) (PSMA) functionalized with amino acids of different hydropathy indices, with the aim of evaluating the effect of the chemical functionality of polyelectrolytes on SH-SY5Y neuroblastoma cell adhesion. Functionalizing PSMA derivatives with l-glutamine, l-methionine, and l-tyrosine yielded PSMA-Gln, PSMA-Met, and PSMA-Tyr polyelectrolytes, respectively. We first studied the adsorption behavior of PSMA functionalized with amino acids on silicon wafer surfaces modified with 3-aminopropyltriethoxysilane at pH 4.0 and 7.0 and at low and high ionic strengths. The highest rate of polyelectrolyte adsorption was at pH 4.0 and high ionic strength and was higher with the glutamine and tyrosine films. The advance contact angles (θA) of the polyelectrolyte surfaces showed a moderate effect of ionic strength and pH on polyelectrolyte film wettability, with PSMA-Tyr being slightly more hydrophobic. Atomic force microscopy images of the polyelectrolyte surfaces showed two types of morphology: the well-defined globular nanostructure of PSMA-Met and PSMA-Tyr and densely packed nanofibrous-like structure of PSMA-Gln. The highest level of ionic strength caused a slight decrease in the size of the nanostructure that formed the surface domains, which was reflected in the degree of surface roughness. Cell adhesion assays with the polyelectrolyte film showed that SH-SY5Y neuroblastoma cells cultured on PSMA-Met present a well-extended morphology characterized by a stellate shape, with five or more actin-rich thin processes, whereas SH-SY5Y cells that were seeded on PSMA-Gln and PSMA-Tyr have a round morphology, with fewer and shorter processes. These results indicate that it is possible to modulate the surface characteristics of polyelectrolyte films based on their chemical functionality and environmental parameters such as pH and ionic strength in order to evaluate their effect on cell adhesion. Thus, surfaces prepared from polyelectrolytes functionalized with amino acids are an attractive and simple platform for cell adhesion, which can be used in developing biomaterials with modulated surface properties.

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib.

BACKGROUND: Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-α and-ß) in patients with advanced GIST following failure of at least imatinib and sunitinib. METHODS: Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. RESULTS: Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR). CONCLUSIONS: Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST.

Utilidad del APE libre en el diagnóstico de cáncer de próstata / Use of free PSA ratio in the diagnosis of prostate cancer

El Cáncer de próstata (CaP) constituye una importante causa de muerte en nuestro país. La razón Antígeno Prostático Específico libre/ Antígeno Prostático Específico total (APE-L/T) es una de las medidas descritas para mejorar la pesquisa de la enfermedad. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo analítico en el Hospital Naval de Viña del Mar entre enero 2007 a diciembre 2011 que incluyó 588 pacientes con biopsias prostáticas que presentaban APE- T entre 2-10 ng/ml. Se evaluó la edad al diagnóstico, el valor de APE-T y la razón APE-L/T en relación al resultado histológico de las biopsias. Se realizaron curvas de rendimiento diagnóstico (ROC) para APE- T y para la razón APE-L/T. Se calculó sensibilidad y especificidad para diferentes puntos de corte para la razón APE-L/T. RESULTADOS: 33 por ciento de las biopsias fueron positivas para CaP. Los valores de la razón APE-L/T fueron significativamente más bajos en pacientes con CaP (p<0.001), alcanzando un área bajo la curva ROC 0,615. El mejor punto de corte para la razón APE-L/T fue de 15 por ciento con una sensibilidad de 60 por ciento y una especificidad de 58 por ciento. Para la razón APE-L/T > 25 por ciento la sensibilidad es 20 por ciento y la especificidad 91 por ciento. En cambio, el APE-T no mostró diferencias estadísticamente significativas (p=0,1) con un AUC 0,55. CONCLUSIONES: El APE-T por sí solo no parece tener capacidad discriminante para detectar CaP cuando los valores se encuentran entre 2-10 ng/ml. La razón APE-L/T tiene una utilidad limitada frente al paciente para decidir efectuar o no una biopsia de próstata.

Prostate cancer (PCa) is one of the major causes of death in our country. The Free/Total Prostate specific antigen ratio (f/t PSA) is one of the measurements that have been used to improve the diagnosis of this disease. MATERIAL AND METHODS: A retrospective analytic study in the Almirante Nef Hospital in Viña del Mar between January 2007 and December 2011 was made, which included 588 patients with prostate biopsies that had tPSA between 2-10 ng/ml. The age at diagnosis was evaluated and the value of tPSA and the f/t PSA ratio were compared with the histological results of the biopsies. Curves were performed for the diagnostic yield (ROC) for tPSA and the f/t PSA ratio. The sensitivity and specificity for different cut-off points for the f/t PSA ratio in the diagnosis of PCa were also calculated. RESULTS: 33 percent of the biopsies were positive for PCa. The f/t PSA ratio values were significantly lower in patients with CaP (p<0.001), reaching an area under the curve of 0,615. The best cutoff for f/t PSA ratio was 15 percent with 60 percent sensitivity and 58 percent specificity. For f/t PSA ratio > 25 percent sensitivity was 20 percent and specificity was 91 percent. PSA showed no statistically significant differences (p = 0.1) with AUC: 0.55. CONCLUSIONS: tPSA alone does not seem to have discriminatory power to detect PCa in patients when values are between 2-10 ng/ml. The f/t PSA ratio has a limited utility to decide to perform a prostate biopsy or not.

Proceso de formulación y validación de las guías alimentarias para la población chilena / Development and validation process of food-based dietary guidelines for the chilean population

The Food Based Dietary Guidelines (FBDG) are educational tools that help people to select appropriate foods for good nutrition and health. Most countries have FBDG's, but its dissemination and implementation have shown weaknesses. This paper presents the development process and validation of the 2012 FBDG for the Chilean population. The latest scientific evidence was reviewed and new messages were validated with METAPLAN, a qualitative-quantitative method for problem analysis applied to information gathered with 48 focus groups from Arica, Santiago and Chillán-Concepción. The messages promote consumption of healthy foods, focusing on critical nutrients (sugar, saturated fats, sodium) and energy intake reduction. Final version of the messages considered comments and suggestions from participants and from two expert panels. Its implementation should include promotion strategies that involve the Ministry of Health, Education, Agriculture, universities, industry and mass media, in order to achieve changes in feeding behavior in the most vulnerable segments of the Chilean population.

Las Guías Alimentarias Basadas en Alimentos (GABA), son instrumentos educativos que ayudan a la población a seleccionar alimentos apropiados para una buena nutrición y salud. La mayoría de los países tienen GABA, pero su difusión e implementación presentan grandes debilidades. Se presenta el proceso para la formulación y validación de las GABA 2012 para la población chilena. Se revisó la evidencia científica reciente y se validaron los mensajes con el Metaplán, método para el análisis de problemas, con 48 grupos focales en Arica, Santiago y Chillán-Concepción. Los mensajes promueven el consumo de alimentos saludables, un menor consumo de energía y de nutrientes críticos. En los mensajes definitivos se incorporó los comentarios y sugerencias de los participantes y de 2 paneles de expertos. Su implementación debería incorporar estrategias de promoción de los Ministerios de Salud, Educación, Agricultura, universidades, la industria y los medios masivos, para lograr cambios en el comportamiento alimentario de los segmentos más vulnerables de la población chilena.

Minocycline increases the life span and motor activity and decreases lipid peroxidation in manganese treated Drosophila melanogaster.

The objective of this study was to investigate the effect of Minocycline in the life span, motor activity, and lipid peroxidation of Drosophila melanogaster treated with manganese. Two days after emerging from the pupa male wild-type D. melanogaster were fed for 13 days with corn media containing 15 mM manganese. Then, they were divided in six groups of 300 flies each: group (a) remained treated with manganese (Mn group); group (b) began treatment with Minocycline (0.05 mM) (Mn-Minocycline group); group (c) received no additional treatment (Mn-no treatment group); group (d) simultaneously fed with manganese and Minocycline (Mn+Minocycline group). Additionally, a control (group e) with no treatment and another group (f) fed only with Minocycline after emerging from the pupa were added. All the manganese treated flies (group a) were dead on the 25th day. The life span in group f (101.66±1.33 days, mean S.E.M.) and of group b (97.00±3.46 days) were similar, but in both cases it was significantly higher than in group e (68.33±1.76 days), group c (67.05±2.30 days) and in those of group d (37.33±0.88). Manganese (groups a and d) decreased motor activity in D. melanogaster. In the Minocycline fed flies (groups b and f) a higher motor activity was detected. In Mn-Minocycline and Mn+Minocycline treated flies a significant decrease of MDA levels was detected when compared to the Minocycline group indicating that Minocycline and Mn appear to have a synergistic effect. In conclusion, Minocycline increased the life span and motor activity and decreased MDA formation of manganese treated D. melanogaster, probably by an inhibition of the production of reactive oxygen species. Manganese also exerted an antioxidant effect as shown by the significant decrease of MDA levels when compared to control flies.

Perfil clínico, epidemiológico y quirúrgico de pacientes operados por cáncer renal en el Hospital Naval Almirante Nef / Clinical, epidemiological and surgical profile of renal cancer patients at Hospital Naval Almirante Nef

Introducción: El cáncer renal ocupa el tercer lugar dentro de los tumores genitourinarios y el 3 por ciento de los tumores malignos primarios, siendo el cáncer urológico con mayor mortalidad y cuya incidencia ha aumentado a nivel mundial. Material y método: Revisión retrospectiva de las fichas de todos los pacientes con diagnóstico de cáncer renal que fueron nefrectomizados o tumorectomizados entre los años 1999 y 2009 en el Hospital Naval Almirante Nef de Viña del Mar, con un total de 135 pacientes. Resultados: Observamos un aumento importante en el número de casos el año 2009, siendo más frecuente en hombres durante los diez años revisados. La media de la edad fue de 61,81 años y la mayoría no presentaba factores de riesgo. Cuarenta y ocho por ciento de los casos diagnosticados fueron hallazgos y 60 por ciento de éstos se encontraban en etapa I. El síntoma más frecuente fue el dolor abdominal. Setenta por ciento de los casos fueron diagnosticados por ecotomografía abdominal y 12 por ciento por pielotac. El 11 por ciento de los pacientes presentaron metástasis posquirúrgicas, siendo la mayoría a pulmón seguido de hígado. De éstos, 20 por ciento habían presentado tumores primarios menores de 7 cm. Conclusión: La incidencia del cáncer renal va en aumento y el diagnóstico precoz de lesiones asintomáticas y de bajo volumen que presentan un porcentaje no despreciable de infiltración tumoral, sugieren un manejo quirúrgico agresivo.

Introduction: Renal cancer represents the third most common cancer within genitourinary tumors and3 percent of all primary malignant tumors. It is the urological cancer with the most mortality rate and it´s incidence has increased worldwide. Methods: Restrospective review of the medical records of every patient diagnosed with renal cancer who where nephrectomized or tumorectomized between the years 1999 and 2009 at Hospital Naval Almirante Nef, Viña del Mar, with a total of 135 patients. Results: There was an important increase in the number of cases in 2009. The higher frequency in men was maintained during the years studied. The mean age was 61.81 years and most of the patients didn’t have any risk factors. 40 percent of the diagnosed cases were asymptomatic findings and 60 percent of them where on stage I. The most frequent symptom was abdominal pain. 70 percent of all cases where diagnosed by abdominal ecotomography and 12 percent CT without contrast. 11 percent of the patients presented post-surgical metastasis, most of them to lung followed by liver. 20 percent of them had primary tumors smaller than 7 cm. Conclusion: The incidence of renal cancer is increasing and the early diagnosis of asymptomatic and small lesions which in an important percentage have tumoral infiltration suggest an aggressive surgical treatment.

Does the availability of single cigarettes promote or inhibit cigarette consumption? Perceptions, prevalence and correlates of single cigarette use among adult Mexican smokers.

BACKGROUND: Single cigarette use and its implications have rarely been studied among adults. OBJECTIVE: To assess perceptions, prevalence and correlates of single cigarette purchase behaviour and its relation to harm reduction. DESIGN: Focus group transcripts and cross-sectional data were analysed. SETTING AND PARTICIPANTS: Focus groups among convenience samples of adult smokers in two Mexican cities and a population-based sample of 1079 adult smokers from the International Tobacco Control Policy Evaluation Project in four Mexican cities. MAIN OUTCOME MEASURES: Purchase of single cigarettes last time cigarettes were bought, frequency of purchasing single cigarettes in the previous month and intention to quit in the next 6 months. RESULTS: Focus group data indicated that smokers bought single cigarettes as a harm reduction strategy. Survey data indicated that 38% of participants purchased single cigarettes in the last month and 10% purchased them the last time they bought cigarettes, with more frequent consumption among young adults and those with lower income. Purchasing single cigarettes was independently associated with the frequency of using single cigarettes to reduce consumption and, less consistently, with the frequency of being cued to smoke after seeing single cigarettes for sale. Using single cigarettes to reduce consumption was positively associated with quit intention, whereas being cued to smoke by single cigarettes was negatively associated with quit intention. CONCLUSIONS: Study results suggest that some adult Mexican smokers purchase single cigarettes as a method to limit, cut down on and even quit smoking. Nevertheless, promotion of the availability of single cigarettes as a harm reduction strategy could provide additional smoking cues that undermine quit attempts and promote youth smoking.

Computerized classification of normal and abnormal lung sounds by multivariate linear autoregressive model.

This work proposes multichannel acquisition of lung sounds by a microphone array, feature extraction by a multivariate AR (MAR) model, dimensionality reduction of the feature vectors (FV) by SVD and PCA and, their classification by a supervised neural network. A microphone array of 25 sensors was attached on the thoracic surface of the subjects, who were breathing at 1.5 L/sec. The supervised neural network used the backpropagation learning algorithm based on the Levenberg-Marquardt rule. Figures of merit for the classification task by the neural net include the percentage of correct classification during training, testing and validation phases as well as sensitivity, specificity and performance. MAR in combination with PCA provided the best average percentage of correct classification with acoustic information not seen by the neural network during the training phase (87.68%). The results state the advantages of a microphone array for the classification of normal and abnormal acoustic pulmonary information in diffuse interstitial pneumonia and for this goal, the authors assume that not only the crackles and their number indicates the severity of the disease, but the basal respiratory signal could be also affected.

Tabaquismo pasivo y asma infantil / Passive smoking and childhood asthma

El humo ambiental del tabaco es un riesgo significativo para la salud de los niños pequeños. Se pretende estudiar el papel del tabaquismo pasivo en el padecimiento de asma en niños expuestos al mismo. Material y métodos: Se realiza un estudio retrospectivo de casos y controles apareados en 835 niños, distribuidos por grupos de edad y sexo. Se elige de forma aleatoria un control por cada caso, realizándose el apareamiento de 482 niños. Se analizan los siguientes factores: convivencia con fumadores, cohabitación con una madre fumadora habitual, presencia de fumadores en el domicilio durante la gestación y tabaquismo materno durante la misma. Los datos se organizan en tablas tetracóricas. Se realiza el test χ2 de Mantel-Haenszel. Se calcula la odds ratio, con intervalo de confianza del 95% y la fracción etiológica del riesgo para cada una de ellas. Resultados: El estudio no demuestra asociación significativa entre presencia habitual de fumadores en el domicilio y mayor frecuencia de asma infantil. En cambio, tener una madre fumadora habitual –especialmente si fuma durante la gestación– y la convivencia de aquélla con fumadores en ese período, sí se asocia significativamente con tal patología. Conclusión: Nuestro estudio pone de manifiesto el riesgo que supone la exposición al humo del tabaco para el desarrollo del asma infantil, determinando una mayor prevalencia de asma en los hijos de mujeres fumadoras –sobre todo si fumaron durante la gestación– y quizás coadyuvando para desencadenar obstrucción bronquial en los que se expusieron al tabaquismo de otras personas en ese período

Environmental tobacco smoke represents a significant risk for children health. The role of passive smoking habit in exposed children suffering from asthma is to be studied. Patients and methods: A retrospective matched casecontrol study is conducted in 835 children, who are distributed in groups according to their age and sex. Acontrol is randomly chosen per each case, thus matching 482 children. The following factors were analyzed: living with smokers, living with an usual smoking mother, usual presence of smokers at home during pregnancy, and maternal smoking habit during pregnancy. Data are arranged in 2x2 tables. χ2 Mantel- Haenszel test is conducted. Odds ratio, with a 95% confidence interval, and ethiological risk fraction are calculated for each one of the studied factors. Results: Our study does not show significant association between usual presence of smokers at home and higher childhood asthma frequency. However, having an usual smoking mother –specially if she smokes during pregnancy– and her living with smokers during this period, do associate significantly with this pathology. Conclusions: Our study reveals the risk that implies the exposure to tobacco smoke for the development of childhood asthma, demonstrating a higher prevalence of asthma in children of smoking mothers –particularly if they smoked during pregnancy– and perhaps contributing to trigger bronchial obstruction in those who were exposed to other people smoking habit during that period

Effect of chronic manganese treatment on adenosine tissue levels and adenosine A2a receptor binding in diverse regions of mouse brain.

In the present study the effects of chronic manganese (Mn) treatment on adenosine A2a receptor binding in mouse brain have been assessed. Male albino mice were divided in two groups: In the Mn-treated group, the animals were injected intraperitoneally (i.p.) with MnCl2 (5 mg/kg/day) five days per week during 9 weeks; in the control group, they were injected likewise with a saline solution. A significant decrease of the Kd without alteration of Bmax in the cerebellum and, an increase of the Kd and Bmax in hippocampus of mice treated with Mn were found. Also, an increase of Kd in frontal cortex was observed. The binding parameters in caudate nucleus, olfactory bulb and hypothalamus were not altered by Mn. A significant decrease in the adenosine concentration in caudate nucleus, olfactory bulb and hypothalamus, without significant changes in hippocampus, frontal cortex and cerebellum was also detected. These findings suggest that chronic administration of Mn could affect adenosine receptor function and turnover, depending on the brain region analyzed.

Synthesis and biological evaluation of aryl azide derivatives of combretastatin A-4 as molecular probes for tubulin.

Two new aryl azides, (Z)-1-(3'-azido-4'-methoxyphenyl)-2-(3",4",5"-trimethoxyphenyl)ethene 9 and (Z)-1-(4'-azido-3'-methoxyphenyl)-2-(3",4",5"-trimethoxyphenyl)ethene 5, modeled after the potent antitumor, antimitotic agent combretastatin A-4 (CA-4), have been prepared by chemical synthesis as potentially useful photoaffinity labeling reagents for the colchicine site on beta-tubulin. Aryl azide 9, in which the 3'-hydroxyl group of CA-4 is replaced by an azido moiety, demonstrates excellent in vitro cytotoxicity against human cancer cell lines (NCI 60 cell line panel, average GI50 = 4.07 x 10(-8) M) and potent inhibition of tubulin polymerization (IC50 = 1.4+/-0.1 microM). The 4'-azido analogue 5 has lower activity (NCI 60 cell line panel, average GI50 = 2.28 x 10(-6) M, and IC50 = 5.2+/-0.2 microM for inhibition of tubulin polymerization), suggesting the importance of the 4'-methoxy moiety for interaction with the colchicine binding site on tubulin. These CA-4 aryl azide analogues also inhibit binding of colchicine to tubulin, as does the parent CA-4, and therefore these compounds are excellent candidates for photoaffinity labeling studies.

[The apolipoprotein E genotype and Down's syndrome]. / Genotipo apolipoproteína E y síndrome de Down.

Some individuals with Down syndrome develop an Alzheimer-type dementia in the third and fourth decades of life. Dementia in Alzheimer disease has been associated with the presence of genotype epsilon 4/epsilon 4 in apolipoprotein E (apo E). By means of molecular analysis techniques genotypes in lipoprotein apo E were identified in 21 patients with Down syndrome. The results obtained showed that 76% of the studied population had the genotype epsilon 3/epsilon 3 and 9% genotypes epsilon 3/epsilon 4 and epsilon 2/epsilon 3. None of the cases was homozygous for the allele epsilon 4. The analysis of our data shows the absence of differences between the distribution of genotype apo E among the Down population studied and among general population. We therefore consider that the presence of the allele epsilon 4 has no influence on the manifestation of Alzheimer disease in patients with Down syndrome.

Ex situ conservation of plant germplasm using biotechnology.

Conservation of plant genetic resources attracts more and more public interest as the only way to guarantee adequate food supplies for future human generations. However, the conservation and subsequent use of such resources are complicated by cultural, economical, technical and political issues. Over the last 30 years, there have been significant increases in the number of plant collections and in accessions in ex situ storage centres throughout the World. The present review is of these ex situ collections and the contribution biotechnology has made and can make to conservation of plant germplasm. The applications and limitations of the new, molecular approaches to germplasm characterization are discussed. In vitro slow growth is used routinely for conserving germplasm of plants such as banana, plantain, cassava and potato. More recently, cryopreservation procedures have become more accessible for long-term storage. New cryopreservation techniques, such as encapsulation-dehydration, vitrification and desiccation, lengthen the list of plant species that can not only tolerate low temperatures but also give normal growth on recovery. Extensive research is still needed if these techniques are to be fully exploited.

Manganese toxicity: muscarinic receptor binding in the mouse brain.

In the present study we determined the effect of repeated administration of manganese chloride on the binding parameters of [3H]quinuclidinyl benzilate (3H-QNB) in striatum, frontal cortex, and hippocampus of mice. Daily intraperitoneal injections of manganese chloride (5 mg Mn/kg) 5 d/wk during 9 wk did not alter the receptor density (Bmax) and the dissociation constant (Kd) of 3H-QNB in the different brain regions studied. These results suggest that chronic treatment with manganese does not affect the binding characteristics of 3H-QNB to the cholinergic muscarinic receptors in mouse brain.